Bachner L, Vinet M C, Lacave R, Babron M C, Rondeau E, Sraer J D, Chevet D, Kaplan J C
INSERM U129. Paris, France.
Hum Genet. 1990 Jul;85(2):221-7. doi: 10.1007/BF00193200.
We describe a large three generation family with autosomal dominant polycystic kidney disease (PKD). Ultrasonographic screening of 60 family members revealed 20 individuals, whose age ranged from ten to eighty years, with one or several cysts in only one kidney and 7 individuals with cysts in both kidneys. Transmission of unilateral cysts seems to be autosomal dominant, although there are some generation gaps. Linkage studies with several markers of the PKD1 locus on the short arm of chromosome 16 showed no linkage with the disease. Lod scores for linkage between the disease and the most informative marker 3'HVR were computed using different penetrance models and several hypotheses concerning the clinical status of individuals with unilateral renal cysts. Results varied from Z = 1.31 to Z = -21.47 (theta = 0). Smith's test of heterogeneity gave a conditional probability of non-linkage between 0.9 and 1.0. We conclude that this family presents a form of autosomal dominant PKD with reduced penetrance and no linkage to the PKD1 locus on the short arm of chromosome 16. Other hypotheses, such as the existence of two distinct hereditary diseases in this large family, or neomutation in one branch of the family associated with a high frequency of isolated renal cysts, are also considered.
我们描述了一个患有常染色体显性遗传性多囊肾病（PKD）的三代大家庭。对60名家庭成员进行超声检查发现，年龄在10岁至80岁之间的20个人仅一侧肾脏有一个或多个囊肿，7个人双侧肾脏都有囊肿。尽管存在一些代际差异，但单侧囊肿的遗传似乎是常染色体显性的。对位于16号染色体短臂上的PKD1位点的几个标记进行连锁研究，结果显示与该疾病无连锁关系。使用不同的外显率模型和关于单侧肾囊肿个体临床状况的几种假设，计算了疾病与信息最丰富的标记3'HVR之间的连锁Lod分数。结果从Z = 1.31到Z = -21.47不等（θ = 0）。史密斯异质性检验得出的非连锁条件概率在0.9到1.0之间。我们得出结论，这个家族呈现出一种外显率降低且与16号染色体短臂上的PKD1位点无连锁关系的常染色体显性PKD形式。我们还考虑了其他假设，例如这个大家庭中存在两种不同的遗传性疾病，或者家族的一个分支中发生了与孤立性肾囊肿高频率相关的新突变。
